CAR-T CELL THERAPY IN ONCOLOGY AND RHEUMATOLOGY

Kornelia Tyczka; Marcin Szczepanik; Maria Nowakowska; Jakub Senko; Joanna Kulpa; Zofia Suchanek

doi:10.31435/ijitss.3(51).2026.6385

Authors

Kornelia Tyczka Independent Public Voivodeship Integrated Hospital in Szczecin, Szczecin, Poland https://orcid.org/0000-0001-8700-2372
Marcin Szczepanik Independent Public Voivodeship Integrated Hospital in Szczecin, Szczecin, Poland https://orcid.org/0009-0004-0475-6187
Maria Nowakowska University Teaching Hospital No. 1 of the Pomeranian Medical University in Szczecin, Poland https://orcid.org/0009-0007-2321-0464
Jakub Senko Pomeranian Medical University in Szczecin, Poland https://orcid.org/0009-0006-2878-5737
Joanna Kulpa Pomeranian Medical University in Szczecin, Poland https://orcid.org/0009-0007-7057-6282
Zofia Suchanek Independent Public Voivodeship Integrated Hospital in Szczecin, Szczecin, Poland https://orcid.org/0009-0003-6911-230X

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.6385

Keywords:

CAR-T Cell Therapy, Hematologic Cancers, Solid Tumors, Systemic Lupus Erythematosus (SLE), Antisynthetase Syndrome

Abstract

Background: CAR-T cell therapy is a highly personalized form of treatment. it involves modifying T cells extracted from the patients white blood cells during cell collection. Genetic modification of said T cells allows for the extraction of chimeric antigen receptor (CAR), which are later multiplied and infused into the recipients organism. The use of such a highly personalized method yields promising results in both oncology and hematology where relapses and the severity of conditions require precise therapy.

Aim: This narrative analysis aims to summarize and explore the present-day application of CAR-T cell therapy, currently held trials and possibilities for future therapy development in the fields of oncology and rheumatology.

Material and methods: A search of relevant research databases was conducted to identify eligible papers.

Results: CAR-T cell therapy shows promising results due to its mechanism of genetical modifications of patients’ own T-cells, thus allowing them to recognize surface antigens present on cancer cells and reduce symptoms and long-term consequences of autoimmune diseases. However, its use still is limited, and more research needs to undergo to better utilize CAR-T cell therapy.

Conclusions: The use of CAR-T cell therapy in oncology and rheumatology is promising however, further studies are needed to assess its efficiency and safety.

References

June, C. H., & Sadelain, M. (2018). Chimeric antigen receptor therapy. New England Journal of Medicine, 379(1), 64–73.

Brudno, J. N., Maus, M. V., & Hinrichs, C. S. (2024). CAR T cells and T-cell therapies for cancer: A translational science review. JAMA, 332(22), 1924–1935.

Chen, L., Xie, T., Wei, B., & Di, D. L. (2022). Current progress in CAR-T cell therapy for tumor treatment. Oncology Letters, 24(4), 358.

Du, B., Qin, J., Lin, B., Zhang, J., Li, D., & Liu, M. (2025). CAR-T therapy in solid tumors. Cancer Cell, 43(4), 665–679.

Mougiakakos, D., Krönke, G., Völkl, S., Kretschmann, S., Aigner, M., Kharboutli, S., et al. (2021). CD19-targeted CAR T cells in refractory systemic lupus erythematosus. New England Journal of Medicine, 385(6), 567–569.

Dingfelder, J., Aigner, M., Taubmann, J., Minopoulou, I., Park, S., & Charles, D. K. J. K. C. T. G. S. A. A. M. (2024). Fully human anti-CD19 CAR T cells derived from systemic lupus erythematosus patients exhibit cytotoxicity with reduced inflammatory cytokine production. Transplantation and Cellular Therapy, 30(6), 582.e1–582.e10.

Ohno, R., & Akihiro, N. (2024). Advancing autoimmune rheumatic disease treatment: CAR-T cell therapies—Evidence, safety, and future directions. Seminars in Arthritis and Rheumatism, 67, 152479.

Wrzesinski, C., & Restifo, N. P. (2005). Less is more: Lymphodepletion followed by hematopoietic stem cell transplant augments adoptive T-cell-based anti-tumor immunotherapy. Current Opinion in Immunology, 17(2), 195–201.

Maude, S. L., Laetsch, T. W., Buechner, J., Rives, S., Boyer, M., Bittencourt, H., et al. (2018). Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. New England Journal of Medicine, 378(5), 439–448.

Neelapu, S. S., Locke, F. L., Bartlett, N. L., Lekakis, L. J., Miklos, D. B., Jacobson, C. A., et al. (2017). Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. New England Journal of Medicine, 377(26), 2531–2544.

Wang, M., Munoz, J., Goy, A., Locke, F. L., Jacobson, C. A., Hill, B. T., et al. (2020). KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. New England Journal of Medicine, 382(14), 1331–1342.

Jacobson, C. A., Chavez, J. C., Sehgal, A. R., William, B. M., Munoz, J., Salles, G., et al. (2022). Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): A single-arm, multicentre, phase 2 trial. Lancet Oncology, 23(1), 91–103.

Munshi, N. C., Anderson, L. D., Shah, N., Madduri, D., Berdeja, J., Lonial, S., et al. (2021). Idecabtagene vicleucel in relapsed and refractory multiple myeloma. New England Journal of Medicine, 384(8), 705–716.

Chen, T., Wang, M., Chen, Y., & Liu, Y. (2024). Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors. Cancer Cell International, 24(1), 133.

Luo, J., & Zhang, X. (2024). Challenges and innovations in CAR-T cell therapy: A comprehensive analysis. Frontiers in Oncology, 14, 1399544.

Adusumilli, P. S., Zauderer, M. G., Rivière, I., Solomon, S. B., Rusch, V. W., O'Cearbhaill, R. E., et al. (2021). A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab. Cancer Discovery, 11(11), 2748–2763.

Bielamowicz, K., Fousek, K., Byrd, T. T., Samaha, H., Mukherjee, M., Aware, N., et al. (2018). Trivalent CAR T cells overcome interpatient antigenic variability in glioblastoma. Neuro-Oncology, 20(4), 506–518.

Depil, S., Duchateau, P., Grupp, S. A., Mufti, G., & Poirot, L. (2020). ‘Off-the-shelf’ allogeneic CAR T cells: Development and challenges. Nature Reviews Drug Discovery, 19(3), 185–199.

Titov, A., Petukhov, A., Staliarova, A., Motorin, D., Bulatov, E., Shuvalov, O., et al. (2018). The biological basis and clinical symptoms of CAR-T therapy-associated toxicites. Cell Death & Disease, 9(9), 897.

Sachdeva, M., Duchateau, P., Depil, S., Poirot, L., & Valton, J. (2019). Granulocyte-macrophage colony-stimulating factor inactivation in CAR T-cells prevents monocyte-dependent release of key cytokine release syndrome mediators. Journal of Biological Chemistry, 294(14), 5430–5437.

Giavridis, T., van der Stegen, S. J. C., Eyquem, J., Hamieh, M., Piersigilli, A., & Sadelain, M. (2018). CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nature Medicine, 24(6), 731–738.

Norelli, M., Camisa, B., Barbiera, G., Falcone, L., Purevdorj, A., Genua, M., et al. (2018). Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nature Medicine, 24(6), 739–748.

Hay, K. A., Hanafi, L. A., Li, D., Gust, J., Liles, W. C., Wurfel, M. M., et al. (2017). Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood, 130(21), 2295–2306.

Alvi, R. M., Frigault, M. J., Fradley, M. G., Jain, M. D., Mahmood, S. S., Awadalla, M., et al. (2019). Cardiovascular events among adults treated with chimeric antigen receptor T-cells (CAR-T). Journal of the American College of Cardiology, 74(25), 3099–3108.

Gupta, S., Seethapathy, H., Strohbehn, I. A., Frigault, M. J., O'Donnell, E. K., Jacobson, C. A., et al. (2020). Acute kidney injury and electrolyte abnormalities after chimeric antigen receptor T-cell (CAR-T) therapy for diffuse large B-cell lymphoma. American Journal of Kidney Diseases, 76(1), 63–71.

Varadarajan, I., & Tamila, L. K.-K. D. W. L. (2020). Management of cytokine release syndrome. In D. W. L. N. N. S. (Ed.), Chimeric antigen receptor T-cell therapies for cancer (pp. 45–64). Elsevier.

Daniel, W. L. R. G. D. L. P. C. U. L. N. A. M. J. S. A. G. C. L. M. (2014). Current concepts in the diagnosis and management of cytokine release syndrome. Blood, 124(2), 188–195.

Gust, J., Ceppi, F., & Cameron, J. T. (2020). Neurotoxicities after CAR T-cell immunotherapy. In D. W. L. N. N. S. (Ed.), Chimeric antigen receptor T-cell therapies for cancer (pp. 83–105). Elsevier.

Poole, K. G. (2019). Patient-experience data and bias—What ratings don’t tell us. New England Journal of Medicine, 380(9), 801–803.

Frühmorgen, P., Wehrmann, K., & Kobras, S. (2000). [Not available]. Internist (Berlin), 41(12), 1382–1390.

Cufi, S., Corominas-Faja, B., Vazquez-Martin, A., Oliveras-Ferraros, C., Dorca, J., Bosch-Barrera, J., et al. (2012). Metformin-induced preferential killing of breast cancer initiating CD44+CD24-/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts. Oncotarget, 3(4), 395–398.

Solé, A., Ciudad, C. J., Chasin, L. A., & Noé, V. (2016). Correction of point mutations at the endogenous locus of the dihydrofolate reductase gene using repair-PolyPurine Reverse Hoogsteen hairpins in mammalian cells. Biochemical Pharmacology, 110–111, 16–24.

Lamperti, M., Hinkelbein, J., Fuchs-Buder, T., & Fitzgerald, R. (2019). Reply to: Anaesthesia and endovascular therapy in patients with acute ischaemic stroke. European Journal of Anaesthesiology, 36(4), 306–307.

Malmborg, K., Enfors-Kautsky, E., Queiroz, C., Norström, A., & Schultz, L. (2021). Operationalizing ecosystem service bundles for strategic sustainability planning: A participatory approach. Ambio, 50(2), 314–331.

Mackensen, A., Müller, F., Mougiakakos, D., Böltz, S., Wilhelm, A., Aigner, M., et al. (2022). Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nature Medicine, 28(10), 2124–2132.

Wang, Q., Xiao, Z. X., Zheng, X., Wang, G., Yang, L., Shi, L., et al. (2025). In vivo CD19 CAR T-cell therapy for refractory systemic lupus erythematosus. New England Journal of Medicine, 393(15), 1542–1544.

Bergmann, C., Müller, F., & Jörg, H. W. D. A. A.-H. G. S. V. M. A. S. K. H. R. T. H. (2023). Treatment of a patient with severe systemic sclerosis (SSc) using CD19-targeted CAR T cells. Annals of the Rheumatic Diseases, 82(8), 1117–1120.

Auth, J., Müller, F., Völkl, S., Bayerl, N., Distler, J. H. W., Tur, C., et al. (2025). CD19-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: A case series. Lancet Rheumatology, 7(2), e83–e93.

Lodka, D., Zschummel, M., Bunse, M., Rousselle, A., Sonnemann, J., Kettritz, R., et al. (2024). CD19-targeting CAR T cells protect from ANCA-induced acute kidney injury. Annals of the Rheumatic Diseases, 83(4), 499–507.

Lodka, D., & Schreiber, A. (2025). CAR-T cells targeting CD19 for the treatment of ANCA vasculitis. Clinical Kidney Journal, 18(Suppl. 2), ii35–ii46.

Freeley, M. (2025). CAR T cell therapy for rheumatoid arthritis. Clinical Reviews in Allergy & Immunology, 68(1), 100.

Kremer, P., Haase, I., Richter, J., Kötter, I., Borie, D., Fehse, B., et al. (2026). A new therapeutic frontier: CD19-targeting CAR-T cell therapy in rheumatoid arthritis: A concise report. Rheumatology, 65(5).